Self-reported lactose intolerance (LI) is frequent in patients with functional bowel disorders (FBD) that could be interpreted as irritable bowel syndrome (IBS). The present study aims to characterize the responses of patients with FBD, without small intestinal bacterial overgrowth (SIBO), and LI, in terms of lactose malabsorption (LM) and lactose sensitivity (LS) according to psychological and clinical features.

Insufficient vitamin D and calcium intake associated with the restricted intake of milk and dairy products can lead to poor health outcomes like malnutrition and abnormal bone mineralization. The aim of the study was to estimate the prevalence of primary and secondary lactose intolerance in children with IBD.

Lactose intolerance (LI) is the symptomatic condition that characterizes subjects unable to digest lactose. The main solution consists of reducing or eliminating lactose from one's diet, and so dairy products, particularly cheeses, are often the first foods excluded. The purpose of this study is to contribute to this topic by creating an updated list of naturally lactose-free (NLF) cheeses. Twenty-five PDO (Protected Designation of Origin) cheeses were selected and analyzed to determine their lactose content. At the same time, interviews with the PDO quality control consortia were carried out to understand which parameters are involved in lactose reduction, based on the cheeses' product specifications. The analytical techniques used here for lactose determination are the most sensitive (HPAEC-PAD and LC/MS-MS), given their low limit of quantification (LOQ) of less than 10 mg/kg. The majority of selected PDO cheeses resulted in a lactose content less than the LOQ. Because of the high variability allowed in PDO cheeses' operative conditions, it would be better to case-by-case examine the PDO cheese specification and declare the product as NLF after repeated analysis. The results of the chemical determination of this research allowed to draw up a very useful list of PDO cheeses for both consumers and nutritionists that could be identified as NLF.

Lactose permease (LacY) from Escherichia coli belongs to the major facilitator superfamily. It facilitates the co-transport of β-galactosides, including lactose, into cells by using a proton gradient towards the cell. We now show that LacY is capable of scrambling glycerophospholipids across a membrane. We found that purified LacY reconstituted into liposomes at various protein to lipid ratios catalyzed the rapid translocation of fluorescently labeled and radiolabeled glycerophospholipids across the proteoliposome membrane bilayer. The use of LacY mutant proteins unable to transport lactose revealed that glycerophospholipid scrambling was independent of H+/lactose transport activity. Unexpectedly, in a LacY double mutant locked into an occluded conformation glycerophospholipid, scrambling activity was largely inhibited. The corresponding single mutants revealed the importance of amino acids G46 and G262 for glycerophospholipid scrambling of LacY.

Lactose synthesis rate is an important factor in milk production and quality in mammals. Understanding the lactose synthesis mechanism is crucial for the improvement of milk quantity and quality. However, research on the temporal gene changes regarding lactose synthesis during the whole lactation is still limited. The objective of this study was to determine gene expression profiles related to lactose synthesis in sows during lactation, and further identify the critical steps or key factors in the lactose synthesis pathway.

Consumption of foods can be suppressed by two feeding system defense mechanisms: conditioned taste aversion (CTA) or taste avoidance learning (TAL). There is a debate in the literature about which form of intake suppression is caused by various aversive stimuli. For instance, illness-inducing stimuli like lithium chloride are the gold standard for producing CTA and external (or peripheral) painful stimuli, such as footshock, are the traditional model of TAL. The distinction between CTA and TAL, which have identical effects on intake, is based on differential effects on palatability. That is, CTA involves a decrease in both intake and palatability, whereas TAL suppresses intake without influencing palatability. We evaluated whether lactose, which causes gastrointestinal pain in adult rats, produces CTA or TAL. Using lick pattern analysis to simultaneously measure intake and palatability (i.e., lick cluster size and initial lick rate), we found that pairing saccharin with intragastric infusions of lactose suppressed both the intake and palatability of saccharin. These results support the conclusion that gastrointestinal pain produced by lactose malabsorption produces a CTA, not TAL as had previously been suggested. Furthermore, these findings encourage the view that the CTA mechanism is broadly tuned to defend against the ingestion of foods with aversive post-ingestive effects.

Trichoderma reesei colonizes predecayed wood in nature and metabolizes cellulose and hemicellulose from the plant biomass. The respective enzymes are industrially produced for application in the biofuel and biorefinery industry. However, these enzymes are also induced in the presence of lactose (1,4-0-ß-d-galactopyranosyl-d-glucose), a waste product from cheese manufacture or whey processing industries. In fact, lactose is the only soluble carbon source that induces these enzymes in T. reesei on an industrial level but the reason for this unique phenomenon is not understood. To answer this question, we used systems analysis of the T. reesei transcriptome during utilization of lactose. We found that the respective CAZome encoded all glycosyl hydrolases necessary for cellulose degradation and particularly for the attack of monocotyledon xyloglucan, from which ß-galactosides could be released that may act as the inducers of T. reesei's cellulases and hemicellulases. In addition, lactose also induces a high number of putative transporters of the major facilitator superfamily. Deletion of fourteen of them identified one gene that is essential for lactose utilization and lactose uptake, and for cellulase induction by lactose (but not sophorose) in pregrown mycelia of T. reesei. These data shed new light on the mechanism by which T. reesei metabolizes lactose and offers strategies for its improvement. They also illuminate the key role of ß-D-galactosides in habitat specificity of this fungus.

Trehalose, a well-known stress-protector of biomolecules, has been investigated for its effect on the mobility, hydration and hydrogen bond interaction of lactose using diffusion-ordered NMR spectroscopy and NMR of hydroxy protons. In ternary mixtures of trehalose, lactose and water, the two sugars have the same rate of diffusion. The chemical shifts, temperature coefficients, vicinal coupling constants and ROE of the hydroxy protons in trehalose, lactose and sucrose were measured for the disaccharides alone in water/acetone-d₆ solutions as well as in mixtures. The data indicated that addition of trehalose did not change significantly the strength of the hydrogen bond interaction between GlcOH3 and GalO5' in lactose. Small upfield shifts were however measured for all hydroxy protons when the sugar concentration was increased. The chemical shift of the GlcOH3 signal in lactose showed less change, attributed to the spatial proximity to GalO5'. Chemical exchange between hydroxy protons of lactose and trehalose was observed in the ROESY NMR spectra. Similar effects were observed with sucrose indicating no specific effect of trehalose at the concentrations investigated (73 to 763 mg/mL) and suggesting that it is the concentration of hydroxy groups more than the type of sugars which is guiding intermolecular interactions.

The short 8-10 amino acid "hinge" sequence in lactose repressor (LacI), present in other LacI/GalR family members, links DNA and inducer-binding domains. Structural studies of full-length or truncated LacI-operator DNA complexes demonstrate insertion of the dimeric helical "hinge" structure at the center of the operator sequence. This association bends the DNA ∼40° and aligns flanking semi-symmetric DNA sites for optimal contact by the N-terminal helix-turn-helix (HtH) sequences within each dimer. In contrast, the hinge region remains unfolded when bound to nonspecific DNA sequences. To determine ability of the hinge helix alone to mediate DNA binding, we examined (i) binding of LacI variants with deletion of residues 1-50 to remove the HtH DNA binding domain or residues 1-58 to remove both HtH and hinge domains and (ii) binding of a synthetic peptide corresponding to the hinge sequence with a Val52Cys substitution that allows reversible dimer formation via a disulfide linkage. Binding affinity for DNA is orders of magnitude lower in the absence of the helix-turn-helix domain with its highly positive charge. LacI missing residues 1-50 binds to DNA with ∼4-fold greater affinity for operator than for nonspecific sequences with minimal impact of inducer presence; in contrast, LacI missing residues 1-58 exhibits no detectable affinity for DNA. In oxidized form, the dimeric hinge peptide alone binds to O1 and nonspecific DNA with similarly small difference in affinity; reduction to monomer diminished binding to both O1 and nonspecific targets. These results comport with recent reports regarding LacI hinge interaction with DNA sequences.

Lactose intolerance (LI) is a common medical problem with limited treatment options. The primary symptoms are abdominal pain, diarrhea, bloating, flatulence, and cramping. Limiting dairy foods to reduce symptoms contributes to low calcium intake and the risk for chronic disease. Adaptation of the colon bacteria to effectively metabolize lactose is a novel and potentially useful approach to improve lactose digestion and tolerance. RP-G28 is novel galacto-oligosaccharide (GOS) being investigated to improve lactose digestion and the symptoms of lactose intolerance in affected patients.

Adult lactase non-persistence (LNP) is due to low lactase expression, resulting in lactose malabsorption (LM). LNP is a genetic trait, but is typically determined by LM markers including breath H2, blood glucose, and urinary galactose after a lactose tolerance test. Known validity of these markers using milk is limited, despite being common practice. Compositional variation, such as β-casein variants, in milk may impact diagnostic efficacy. This study aimed to evaluate the diagnostic accuracy to detect LNP using these commonly measured LM markers after both lactose and milk challenges.

The discovery of molecules that can inhibit the action of phytopathogens is essential to find alternative to current pesticides. Pectin methylesterases (PME), enzymes that fine-tune the degree of methylesterification of plant cell wall pectins, play a key role in the pathogenicity of fungi or bacteria. Here we report the synthesis of new lactoside derivatives and their analysis as potential PME inhibitors using three plants and one fungal PME. Because of its structure, abundance and reduced cost, lactose was chosen as a case study. Lactoside derivatives were obtained by TEMPO-mediated oxidation of methyl lactoside, followed by an esterification procedure. Three derivatives were synthesized: sodium (methyl-lactosid)uronate, methyl (methyl-lactosid)uronate and butyl (methyl-lactosid)uronate. The inhibition of the plant and pathogen enzyme activities by lactoside derivatives was measured in vitro, showing the importance of the substitution on lactose: methyl (methyl-lactosid)uronate was more efficient than butyl (methyl-lactosid)uronate. These results were confirmed by docking analysis showing the difference in the interaction between lactoside derivatives and PME proteins. In conclusion, this study identified novel inhibitors of pectin remodeling enzymes.

Lactose has become the main byproduct of many dairy products and ingredients. Current applications of lactose are insufficient to use the recovered lactose from manufacturing operations. Here we exemplified a new process for converting aqueous lactose into a sweeting syrup via one-pot synthesis. The synthesis consisted of two-steps: (1) enzymatic hydrolysis of lactose and (2) catalytic isomerization over MgO/SiO2. The hydrolysis of lactose over β-galactosidase converted 95.77 ± 0.67% of lactose into glucose and galactose. The catalytic isomerization was performed over MgO/SiO2 with different MgO loadings (10-40 wt.%). A battery of tests was conducted to characterize the different catalysts, including surface properties, basicity, and microstructure. The one-pot synthesis, enzymatic hydrolysis and catalytic isomerization over 20%-MgO/SiO2, converted 99.3% of lactose into a sweetening syrup made of glucose (30.48%), galactose (33.51%), fructose (16.92%), D-tagatose (10.54%), and lactulose (3.62%). The outcomes of this research present an opportunity for expanding the utilization of lactose.

Lactose malabsorption occurs in around 68% of the world's population, causing lactose intolerance (LI) symptoms, such as abdominal pain, bloating, and diarrhea. To alleviate LI, previous studies have mainly focused on strengthening intestinal β-galactosidase activity while neglecting the inconspicuous drop in the colon pH caused by the fermentation of non-hydrolyzed lactose by the gut microbes. A drop in colon pH will reduce the intestinal β-galactosidase activity and influence intestinal homeostasis.

Irritable bowel syndrome (IBS) affects 10%-20% of the adult population and is characterized by abdominal symptoms without relevant organic disease. There are numerous clinical trials available investigating the relationship between IBS, lactose maldigestion (LM), and lactose intolerance (LI), but there have been no meta-analyses on this topic yet. We aimed to assess the prevalence of LM, objective and subjective (self-reported) LI in IBS patients compared to healthy controls (HC) without IBS.

Galectin-4 is a tandem-repeat galectin with two distinct carbohydrate recognition domains (CRD). Galectin-4 is expressed mainly in the alimentary tract and is proposed to function as a lipid raft and adherens junction stabilizer by its glycan cross-linking capacity. Galectin-4 plays divergent roles in cancer and inflammatory conditions, either promoting or inhibiting each disease progression, depending on the specific pathological condition. The study of galectin-4's ligand-binding profile may help decipher its roles under specific conditions. Here we present the X-ray structures of human galectin-4 N-terminal CRD (galectin-4N) bound to different saccharide ligands. Galectin-4's overall fold and its core interactions to lactose are similar to other galectin CRDs. Galectin-4N recognises the sulfate cap of 3'-sulfated glycans by a weak interaction through Arg45 and two water-mediated hydrogen bonds via Trp84 and Asn49. When galectin-4N interacts with the H-antigen mimic, 2'-fucosyllactose, an interaction is formed between the ring oxygen of fucose and Arg45. The extended binding site of galectin-4N may not be well suited to the A/B-antigen determinants, α-GalNAc/α-Gal, specifically due to clashes with residue Phe47. Overall, galectin-4N favours sulfated glycans whilst galectin-4C prefers blood group determinants. However, the two CRDs of galectin-4 can, to a less extent, recognise each other's ligands.

Escherichia coli is a well-studied anaerobic bacteria which is able to regulate metabolic pathways depending on the type of sugar presented in the medium. We have studied the glucose-lactose shift in E. coli at the protein level using a recently developed mass spectrometry platform.

The simultaneous production of lactulose (LAU), lactobionic acid (LBA), and organic acids from sweet and acid whey permeate (SWP and AWP) via catalytic synthesis (5% Ru/C) was studied in a continuous stirred-tank reactor. At selected conditions (60 °C, 60 bar, and 600 rpm), a maximum conversion of lactose (37 and 34%) was obtained after 90 min for SWP and AWP, respectively. The highest yield calculated with respect to the initial concentration of lactose for LAU was 22.98 ± 0.81 and 15.29 ± 0.81% after only 30 min for SWP, and AWP, respectively. For LBA, a maximum yield was found in SWP (5.23%) after 210 min, while about 2.2% was found in AWP. Six major organic acids (gluconic, pyruvic, lactic, formic, acetic, and citric acid) were quantified during the one-pot synthesis of lactose.

Galectin-10 (Gal-10) forms Charcot-Leyden crystals (CLCs), which play a key role in the symptoms of asthma and allergies and some other diseases. Gal-10 has a carbohydrate-binding site; however, neither the Gal-10 dimer nor the CLCs can bind sugars. To investigate the monomer-dimer equilibrium of Gal-10, high-performance size-exclusion chromatography (SEC) was employed to separate serial dilutions of Gal-10 with and without carbohydrates. We found that both the dimerization and crystallization of Gal-10 were promoted by lactose/galactose binding. A peak position shift for the monomer was observed after treatment with either lactose or galactose, implying that the polarity of the monomer was reduced by lactose/galactose binding. Further experiments indicated that alkaline conditions of pH 8.8 mimicked the lactose/galactose-binding environment, and the time interval between monomers and dimers in the chromatogram decreased from 0.8 min to 0.4 min. Subsequently, the electrostatic potential of the Gal-10 monomers was computed. After lactose/galactose binding, the top side of the monomer shifted from negatively charged to electrically neutral, allowing it to interact with the carbohydrate-binding site of the opposing subunit during dimerization. Since lactose/galactose promotes the crystallization of Gal-10, our findings implied that dairy-free diets (free of lactose/galactose) might be beneficial to patients with CLC-related diseases.

The sugar transporter Lactose permease (LacY) of Escherichia coli has become a prototype to understand the underlying molecular details of membrane transport. Crystal structures have trapped the protein in sugar-bound states facing the periplasm, but with narrow openings unable to accommodate sugar. Therefore, the molecular details of sugar uptake remain elusive. In this work, we have used extended simulations and metadynamics sampling to explore a putative sugar-uptake pathway and associated free energy landscape. We found an entrance at helix-pair 2 and 11, which involved lipid head groups and residues Gln 241 and Gln 359. Furthermore, the protein displayed high flexibility on the periplasmic side of Phe 27, which is located at the narrowest section of the pathway. Interactions to Phe 27 enabled passage into the binding site, which was associated with a 24 ± 4 kJ/mol binding free energy in excellent agreement with an independent binding free energy calculation and experimental data. Two free energy minima corresponding to the two possible binding poses of the lactose analog β-D-galactopyranosyl-1-thio-β-D-galactopyranoside (TDG) were aligned with the crystal structure-binding pocket. This work outlines the chemical environment of a putative periplasmic sugar pathway and paves way for understanding substrate affinity and specificity in LacY.